Vestibular impairment and adaptive postural imbalance in parkinsonian patients with lateral trunk flexion

Lateral trunk flexion is a very common clinical observation in patients affected by Parkinson's disease. Postural control is known to depend on vestibular, visual, and somatosensory information. The aim of this study was to investigate whether impairment of vestibular function can account for the postural alterations observed in parkinsonian patients with lateral trunk flexion. We evaluated vestibular function in 11 parkinsonian patients with lateral trunk flexion and in 11 age‐, sex‐, and disease duration–matched patients without lateral trunk flexion. The following vestibular tests were performed: infrared videonystagmography including fast and slow ocular movements, spontaneous‐positional and evoked nystagmus search with and without visual fixation, fast positioning maneuvers, the bithermal caloric test, and the vibration test. A peripheral, unilateral vestibular hypofunction was identified in all patients with lateral trunk flexion. The vestibular hypofunction was ipsilateral to the leaning side and contralateral to the most affected parkinsonian side in all patients. In the control group, 7 subjects had no vestibular signs; 4 subjects had unilateral vestibular hypofunction without clinically evident lateral trunk flexion. Two of the latter patients subsequently developed lateral trunk flexion ipsilateral to the vestibular deficit and contralateral to the side most affected by Parkinson's disease. The processing of vestibular information was impaired in parkinsonian patients affected by lateral trunk flexion. The impairment was at least in part responsible for the patients' postural abnormality. We propose that the acronym PISA (Postural Imbalance Syndrome with vestibular Alterations) be used to describe the specific postural change observed in parkinsonian patients affected by a vestibular defect and lateral trunk flexion. © 2011 Movement Disorder Society     

Origin of vestibular dysfunction in Usher syndrome type 1B

It is still debated to what extent the vestibular deficits in Usher patients are due to either central vestibulocerebellar or peripheral vestibular problems. Here, we determined the origin of the vestibular symptoms in Usher 1B patients by subjecting them to compensatory eye movement tests and by investigating the shaker-1 mouse model, which is known to have the same mutation in the myosin-VIIa gene as Usher 1B patients. We show that myosin-VIIa is not expressed in the human or mouse cerebellum and that the vestibulocerebellum of both Usher 1B patients and shaker-1 mice is functionally intact in that the gain and phase values of their optokinetic reflex are normal. In addition, Usher 1B patients and shaker-1 mice do not show an angular vestibuloocular reflex even though eye movement responses evoked by electrical stimulation of the vestibular nerve appear intact. Finally, we show histological abnormalities in the vestibular hair cells of shaker-1 mice at the ultrastructural level, while the distribution of the primary vestibular afferents and the vestibular brainstem circuitries are unaffected. We conclude that the vestibular dysfunction of Usher 1B patients and shaker-1 mice is peripheral in origin.     

Postural disturbance in patients with normal pressure hydrocephalus

The postural function in 52 patients with normal pressure hydrocephalus (NPH) and in 19 patients with subcortical arteriosclerotic encephalopathy (SAE) was analysed bedside and in 17 of the NPH, 10 of the SAE and 23 healthy individuals (HI) also examined with a force platform. At the bedside examination, no differences in postural functions between NPH and SAE patients were found. The NPH patients improved more in the postural than in motor functions after shunt surgery. The NPH patients had a larger sway area and a higher backward directed velocity of centre of pressure than HI. The direction of the inclination in the sagittal plane was neutral or forward in the NPH and the SAE patients while it was backward in HI. The postural function was better in positions with open eyes in all 3 groups, but significantly less in the NPH patients, indicating a misinterpretation of afferent visual stimuli in the brainstem postural centre.     

Developmental perspective of sensory organization on postural control

The development of sensory organization on postural control was studied using computerized dynamic posturography. Generalized postural stability increased with age but had not reached the adult level at the age of 15 years. The significance of each sensory component for postural control was analysed. Somatosensory function developed early and become comparable with the adult level at the age of 3–4 years. The visual function followed and reached the adult level at the age of 15 years. The vestibular function developed later, showing a considerably lower level even at the age of 15 years. Girls were superior to boys with respect to the vestibular function at the age of 7–8 years. The implication of this sexual difference for some developmental disorders is discussed.     

How the eyes move the body

The increased postural sway of patients with disorders of the vestibular system improves with vision. The suppression of pathologic nystagmus also reduces sway. Because the latter effect cannot be attributed to retinal slip as a relevant feedback for postural control, the authors investigated how eye movements rather than retinal slip affect balance. They found that slow eye movements increase sway, possibly by an efference copy, which explains why spontaneous nystagmus causes postural imbalance.     

Drug-resistant temporal lobe epilepsy is associated with postural control abnormalities

Epilepsy is responsible for falls that are not systematically associated with seizures and that therefore suggest postural impairment. There are very few studies of postural control in patients with epilepsy and none of them focus on temporal lobe epilepsy (TLE), although part of the vestibular cortex is located in the temporal cortex. The aim of this study was to evaluate the characteristics of postural control in a homogeneous population of patients with complex partial TLE. Twenty-six patients with epilepsy and 26 age-matched healthy controls underwent a sensory organization test combining six conditions, with and without sensory conflicting situations. Patients with epilepsy displayed poorer postural control, especially in situations where vestibular information is necessary to control balance. In addition to potential antiepileptic drug side effects, vestibular dysfunction could be related to the temporal pathology. Our study allows for a better understanding of the mechanism underlying falls in this population of patients.     

Regional differences of brain glucose metabolic compensation after unilateral labyrinthectomy in rats: a [14C]2-deoxyglucose study

A unilateral labyrinthectomy was performed on anesthetized adult albino rats. Brain [14C]2-deoxyglucose (2DG) uptake was measured autoradiographically 3.5 h to 20 days later and compared to sham-operated controls. In the vestibular nuclei (nn.) of labyrinthectomized subjects, large left-right differences of 2DG uptake occurred, which decreased over time. The equalization of vestibular nuclear 2DG uptake paralleled behavioral compensation of body, neck and head postural abnormalities, and known equalization of vestibular nuclear cell firing rates during compensation. There was a small difference of 2DG uptake in medial and lateral vestibular nn. 20 days after lesions when animals had a residual head tilt and tonic eye deviation. In the oculomotor nn., trochlear nn. and interstitial n. of Cajal, large left-right differences of 2DG uptake occurred, which did not change over time. The higher 2DG uptake in these nn. occurred ipsilateral to the labyrinthine lesion and did not correlate with the onset and cessation of nystagmus. The persistent asymmetry did appear to correlate with ipsilateral downward and contralateral upward eye deviation which continued for long periods after the lesion. We hypothesize that the non-compensating metabolic asymmetry in the oculomotor and trochlear nn. could be due to lesioned otolithic input to the vestibular nn. which relays to trochlear and oculomotor nn.     

General vestibular testing.

A dysfunction of the vestibular system is commonly characterized by a combination of phenomena involving perceptual, ocular motor, postural, and autonomic manifestations: vertigo/dizziness, nystagmus, ataxia, and nausea. These 4 manifestations correlate with different aspects of vestibular function and emanate from different sites within the central nervous system. The diagnosis of vestibular syndromes always requires interdisciplinary thinking. A detailed history allows early differentiation into 9 categories that serve as a practical guide for differential diagnosis: (1) dizziness and lightheadedness; (2) single or recurrent attacks of vertigo; (3) sustained vertigo; (4) positional/positioning vertigo; (5) oscillopsia; (6) vertigo associated with auditory dysfunction; (7) vertigo associated with brainstem or cerebellar symptoms; (8) vertigo associated with headache; and (9) dizziness or to-and-fro vertigo with postural imbalance. A careful and systematic neuro-ophthalmological and neuro-otological examination is also mandatory, especially to differentiate between central and peripheral vestibular disorders. Important signs are nystagmus, ocular tilt reaction, other central or peripheral ocular motor dysfunctions, or a unilateral or bilateral peripheral vestibular deficit. This deficit can be easily detected by the head-impulse test, the most relevant bedside test for the vestibulo-ocular reflex. Laboratory examinations are used to measure eye movements, to test semicircular canal, otolith, and spatial perceptional function and to determine postural control. It must, however, be kept in mind that all signs and ocular motor and vestibular findings have to be interpreted within the context of the patient's history and a complete neurological examination.     

Vestibular compensation: analysis of postural re-arrangement as a control index for unilateral vestibular deficit

Patients with an acute unilateral vestibular lesion show an impaired balance control. The initial presentation is vertigo followed by postural instability; but with time, the global balance functions can be completely restored by a process called vestibular compensation. The aim of our study was to evaluate short and long-term variations of postural parameters in 20 patients affected by vestibular neuritis (VN), and to compare these patients to 20 normal individuals using computerized static posturography (CSP) along with patient feedback throughout the spectral frequency analysis. This analysis showed in patients with no residual dizziness a frequency shift of body sway from low to middle frequencies as a probable expression of the compensatory strategies used by the central nervous system. On the other hand, patients with persistence of postural instability did not show any frequency shift. Our results seem to provide an early index of a proper occurring compensation so that we can adjust therapeutic protocols according to each patient's functional modifications.     

Vestibular syndromes in the roll plane: Topographic diagnosis from brainstem to cortex

Central vestibular syndromes may be classified according to the three major planes of action of the vestibuloocular reflex, secondary to a lesional tone imbalance in either the horizontal yaw plane or the vertical pitch or roll plane. The clinical signs, both perceptual and motor, of a vestibular tone imbalance in the roll plane are ocular tilt reaction (OTR), ocular torsion, skew deviation and tilts of the perceived visual vertical (SVV). Either complete OTR or skew torsion without head tilt indicates a unilateral peripheral deficit of otolith input or a unilateral lesion of graviceptive brainstem pathways from the vestibular nuclei (crossing midline at the pontine level) to the interstitial nucleus of Cajal (INC) in the rostral midbrain. SVV tilts are the most sensitive sign of a vestibular tone imbalance in roll and occur with peripheral or central vestibular lesions from the labyrinth to the vestibular cortex. All tilt effects, perceptual, ocular motor and postural, are ipsiversive (ipsilateral eye undermost) with unilateral peripheral or pontomedullary lesions below the crossing of the graviceptive pathways. All tilt effects are contraversive (contralateral eye undermost) with unilateral pontomesencephalic brainstem lesions and indicate involvement of the medial longitudinal fasciculus or the rostral midbrain (INC). Unilateral lesions of vestibular structures rostral to the INC typically manifest with deviations of perceived vertical without concurrent eye–head tilt. OTR in unilateral paramedian thalamic infarctions indicates simultaneous ischemia of the paramedian rostral midbrain including the INC. Unilateral lesions of the posterolateral thalamus can cause thalamic astasia and moderate ipsiversive or contraversive SVV tilts, thereby indicating involvement of the vestibular thalamic subnuclei. Unilateral lesions of the parietoinsular vestibular cortex cause moderate, mostly contraversive SVV tilts. An SVV tilt found with monocular but not with binocular viewing is typical for a trochlear or oculomotor palsy rather than a supranuclear graviceptive brainstem lesion.     

A dynamic model for eye‐position‐dependence of spontaneous nystagmus in acute unilateral vestibular deficit (Alexander's Law)

Spontaneous nystagmus (SN) is a symptom of acute vestibular tone asymmetry. Alexander's Law (AL) states that slow‐phase velocity of SN is higher when looking in the direction of fast‐phases of nystagmus and lower in the slow‐phase direction. Earlier explanations for AL predict that during SN, slow‐phase eye velocity is a linear function of eye position, increasing linearly as eye deviates towards the fast‐phase direction. Recent observations, however, show that this is often not the case; eye velocity does not vary linearly with eye position. Such new findings necessitate a re‐evaluation of our understanding of AL. As AL may be an adaptive response of the vestibular system to peripheral lesions, understanding its mechanism could shed light on early adaptation strategies of the brain. Here, we propose a physiologically plausible mechanism for AL that explains recent experimental data. We use a dynamic control system model to simulate this mechanism and make testable predictions. This mechanism is based on the known effects of unilateral vestibular deficit on the response of the ipsi‐ and contralesional vestibular nuclei (VN) of the brainstem. This hypothesis is based on the silencing of the majority of ipsilesional VN units, which creates an asymmetry between the responses of the ipsi‐ and contralesional VN. Unlike former explanations, the new hypothesis does not rely on lesion detection strategies or signals originating in higher brain structures. The proposed model demonstrates possible consequences of acute peripheral deficits for the function of the velocity‐to‐position neural integrator of the ocular motor system and the vestibulo‐ocular reflex.     

Regional differences of brain glucose metabolic compensation after unilateral labyrinthectomy in rats: a [C]2-deoxyglucose study

A unilateral labyrinthectomy was performed on anesthetized adult albino rats. Brain [¹⁴C]2-deoxyglucose (2DG) uptake was measured autoradiographically 3.5 h to 20 days later and compared to sham-operated controls. In the vestibular nuclei (nn.) of labyrinthectomized subjects, large left-right differences of 2DG uptake occurred, which decreased over time. The equalization of vestibular nuclear 2DG uptake paralleled behavioral compensation of body, neck and head postural abnormalities, and known equalization of vestibular nuclear cell firing rates during compensation. There was a small difference of 2DG uptake in medial and lateral vestibular nn. 20 days after lesions when animals had a residual head tilt and tonic eye deviation. In the oculomotor nn., trochlear nn. and interstitial n. of Cajal, large left-right differences of 2DG uptake occurred, which did not change over time. The higher 2DG uptake in these nn. occurred ipsilateral to the labyrinthine lesion and did not correlate with the onset and cessation of nystagmus. The persistent asymmetry did appear to correlate with ipsilateral downward and contralateral upward eye deviation which continued for long periods after the lesion. We hypothesize that the non-compensating metabolic asymmetry in the oculomotor and trochlear nn. could be due to lesioned otolithic input to the vestibular nn. which relays to trochlear and oculomotor nn.     

Absence of nystagmus during REM sleep in patients with vestibular neuritis

Saccades, including fast phases of nystagmus, disappear during drowsiness and non-rapid eye movement (NREM) sleep, but are present during the alert state and REM sleep. The purpose of this study was to determine whether spontaneous nystagmus is present in patients with vestibular neuritis during REM sleep. Eight patients with spontaneous nystagmus due to vestibular neuritis and eight control patients without any nystagmus underwent at least one night of polysomnography. Fast phases of nystagmus were analyzed. The number of right and left horizontal saccades were counted, first during 3-5 minute samples of the awake state before sleep onset, then during the first REM episode and the last REM episode of nocturnal sleep, and finally during the alert state in the morning after nocturnal sleep. All patients with vestibular neuritis showed significantly more saccades (fast phases) towards the side contralateral to their vestibular lesion in the awake state before and after the polysomnography. This reflects their spontaneous nystagmus. By contrast, during REM sleep the patients with vestibular neuritis showed no preponderance in saccade direction. The eye movement pattern in REM was the same for patients and controls. In conclusion, peripheral vestibular imbalance producing nystagmus in vestibular neuritis in the awake state is not active at the brain stem level during REM sleep.     

Wallenberg's syndrome: lateropulsion, cyclorotation, and subjective visual vertical in thirty-six patients.

We measured the subjective visual vertical, cyclorotation of the eyes, and head and body lateropulsion in 36 patients with Wallenberg's syndrome. All patients exhibited significant tilts of the internal representation of the gravity vector, as indicated by deviation of subjective visual vertical ipsiversive to the lesion. Most patients (82%) had ipsiversive cyclorotation of one or both eyes, especially excyclotropia of the eye ipsilateral to the brainstem lesion. Twelve of 36 patients (33%), those with the most severe body lateropulsion, had a complete ocular tilt reaction consisting of head tilt, skew deviation, and cyclorotation in the roll plane. We hypothesize that deviation of subjective visual vertical, lateropulsion of the body, and cyclorotation of the eyes are the perceptual, the ocular motor, and the postural consequences of a common lesion of central vestibular pathways that subserve the vestibuloocular reflex in the roll plane. Lateropulsion in patients with Wallenberg's syndrome is interpreted as a postural consequence of an abnormal tilt of the internal representation of orientation in space.     

Both actual and imagined locomotion suppress spontaneous vestibular nystagmus

Acute unilateral vestibulopathy is characterized by a combination of signs and symptoms including spontaneous nystagmus, postural imbalance and gait disturbance. A functional link between these vestibulo-ocular and vestibulo-spinal motor responses has been demonstrated. These responses use common vestibular input and partially overlapping neuronal networks, but it is not known if and to what extent they are linked or operate separately. We found that slow phase velocity of spontaneous vestibular nystagmus in patients with acute vestibulopathy was suppressed by 26% during actual walking (ANOVA p< 0.02, = 6). It was also suppressed by imagined locomotion: by 26% during the imagination of walking and by 42% during the imagination of running ( p< 0.003, = 10). The suppression of vestibular nystagmus might be beneficial for patients, for it alleviates the disturbing impression of movement of the visual scene (oscillopsia) caused by involuntary eye movements.     

Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder with prominent eye movement deficits localizing to the cerebellum. We sought to determine if 4-aminopyridine (4-AP), which putatively enhances the precision of Purkinje neurons, could improve the disorders of eye movements and vestibular function in A-T. The influence of 4-AP on disorders of eye movements and vestibular function was studied in four A-T patients. The effects on the cerebellar control of vestibulo-ocular reflex (VOR) was quantitatively assessed by the decay time constant of per- and post-rotational nystagmus during constant velocity en bloc rotations. The length of the VOR time constant determines the fidelity of the vestibular velocity storage, a neural mechanism that increases the bandwidth of VOR under cerebellar control. The VOR time constant was not increased in A-T patients. The latter is explained by the extent of cerebellar lesion as previously described in A-T and other cerebellar disorders. Nevertheless, 4-AP shortened the VOR time constant during horizontal rotations. Severe disinhibition of velocity storage in subjects with putatively profound cerebellar degeneration manifest periodic alternating nystagmus (PAN). Among two A-T subjects who manifested PAN, 4-AP reduced the peak slow phase velocity of the more severely affected individual and abrogated the PAN in the other. Two A-T subjects manifested horizontal and vertical spontaneous nystagmus (SN) in primary gaze, 4-AP reduced its slow phase velocity. We conclude that in subjects with A-T 4-AP has a prominent effect on the ocular motor and vestibular deficits that are ascribed to the loss of cerebellar Purkinje neurons.     

Vestibular testing by electrical stimulation in patients with unilateral vestibular deafferentation: galvanic evoked myogenic responses testing versus galvanic body sway testing.

OBJECTIVE: To investigate the agreement of a lesion site as indicated by two different vestibular tests with electrical stimulation, galvanic body sway testing (GBST) and galvanic evoked myogenic responses (galvanic vestibular evoked myogenic potential; galvanic VEMP) testing, in patients with unilateral vestibular deafferentation. METHODS: Nineteen patients with unilateral vestibular deafferentation were studied, and the criteria for patient selection were as follows: (1) absence of a caloric response to ice water on the affected side in a supine position, and (2) absence of VEMP to 95 dBnHL clicks on the affected side. We assessed the postural response of the subjects to long duration galvanic stimulation (1 mA, 5 s) by measuring the lateral displacement at the center of foot pressure with a cathode electrode on the forehead, and an anode electrode on the mastoid (GBST). We also recorded the electromyographic (EMG) activities of the sternocleidomastoid muscle (SCM) to short duration galvanic stimulation (3 mA, 1 ms) (galvanic VEMP) with a cathode electrode on the mastoid, and an anode electrode on the forehead. RESULTS: In 18 of the 19 patients, the lesion site indicated by GBST was identical to that indicated by galvanic VEMP. Fourteen patients had abnormal results in both tests while 4 patients had normal results in both tests. One patient with acoustic neuroma had normal results in GBST but abnormal results in galvanic VEMP. CONCLUSIONS: These results suggest that electrical stimulation in these two tests stimulates the same area of the peripheral vestibular afferent system, although the duration of stimulation was different, and that the estimate of the lesion site indicated by these tests in patients with complete or nearly complete unilateral vestibular damages is reliable. SIGNIFICANCE: These results suggest that short-duration galvanic stimulation as well as long-duration galvanic stimulation stimulates the vestibular system at the same level.     

The vestibular control of balance after stroke

OBJECTIVES: To examine vestibular control of balance in those who recovered the ability to stand after middle cerebral artery (MCA) stroke. METHODS: Sixteen patients with MCA stroke were compared with 10 age matched controls. Two additional patients were studied with isolated corticospinal tract lesions, one each at the level of the pons and medulla. Vestibular evoked postural responses were obtained using galvanic vestibular stimulation (GVS) while patients stood with their eyes closed and head facing forwards, equally loading both legs. The GVS response was characterised by measuring the amplitude of the stimulus evoked lateral forces acting through each leg and the lateral displacement of the axial skeleton. RESULTS: Lateral displacement and net lateral force following GVS were significantly larger after stroke. Unlike controls, the lateral forces in the stroke group were asymmetrical, being enhanced on the side of the non-paretic limb and small on the side of the paretic limb. The degree of GVS evoked asymmetry correlated with corticospinal damage assessed using transcranial magnetic stimulation. A similar asymmetrical response was seen in the patient with the pontine lesion but not the patient with the medullary lesion. CONCLUSIONS: MCA stroke may disrupt corticobulbar projections to brainstem output pathways involved in vestibular control of balance. These projections are either collaterals of the corticospinal tract or lie close to that tract and terminate in the pons/upper medulla. This hypothesis accounts for the association between corticospinal tract damage and GVS response asymmetry, and the lack of GVS evoked asymmetry with corticospinal lesions below the rostral medulla.     

A topodiagnostic investigation on body lateropulsion in medullary infarcts

Body lateropulsion may occur without signs of vestibular dysfunction and vestibular nucleus involvement. The authors examined 10 such patients with three-dimensional brainstem mapping. Body lateropulsion without limb ataxia reflected an impairment of vestibulospinal postural control caused by a lesion of the descending lateral vestibulospinal tract, whereas body lateropulsion with limb ataxia was probably the consequence of impaired or absent proprioceptive information caused by a lesion of the ascending dorsal spino-cerebellar tract.     

'PREHAB': Vestibular prehabilitation to ameliorate the effect of a sudden vestibular loss

A sudden unilateral loss or impairment of vestibular function causes vertigo, dizziness and impaired postural function. In most occasions, everyday activities supported or not by vestibular rehabilitation programs will promote compensation and the symptoms subside. As the compensatory process requires sensory input, matching performed motor activity, both motor learning of exercises and matching to sensory input are required. If there is a simultaneous cerebellar lesion found during surgery of the posterior cranial fossa, there may be a risk of a combined vestibulo-cerebellar lesion, with reduced compensatory abilities and with prolonged or sometimes permanent disability. On the other hand, a slow gradual loss of unilateral function occurring as the subject continues well everyday activities may go without any prominent symptoms. We therefore implemented a pre treatment plan before planned vestibular lesions (prehab). This was first done in subject undergoing gentamicin treatment for Meniere's disease (MD). Subjects perform vestibular exercises for 14 days before the first gentamicin installation and then continue doing so until free of symptoms. Most subjects would only experience slight dizziness while losing vestibular function. We then expanded the approach to patients with brainstem tumours requiring surgery but with remaining vestibular function to ease postoperative symptoms and reduce risk of combined cerebello-vestibular lesions. This patient group was given gentamicin installations trans-tympanically before tumour sugary and then underwent prehab. In all cases there was a caloric loss, loss of VOR evident in the head impulse tests, impaired subjective vertical and horizontal, and reduced caloric function induced by the pre-surgery gentamicin treatment. The prehab eliminated spontaneous and positional nystagmus, subjective symptoms, and postural function up before surgery and allowed for rapid postoperative recovery.The concept of 'pre-lesion rehabilitation' where training is introduced before a planned lesion and if possible paralleled with a gradual function loss expands the potential of rehabilitation. Here it was used for vestibular lesions but it is possible that similar approaches may be developed for other situations, which include foreseeable loss of function.